Safety and efficacy of intraperitoneal perfusion with tumor vesicle-encapsulated methotrexate for the treatment of cancerous ascites - an open, randomized and controlled clinical trial

摘要

Background: Cancerous ascites is a common and severe complication that occurs in patients with late-stagemalignant tumors. The prognosis of cancerous ascites is poor, clinical treatment is difficult and therapeutic outcomeis disappointing. In the present study, tumor cell-derived vesicles were used as drug delivery vehicles thatencapsulated a chemotherapeutic agent and were perfused into a patients’ abdominal cavity to effectively kill thecancer cells in cancerous ascites. Pre-clinical data has demonstrated that tumor vesicles that carry low-dosechemotherapeutics can efficiently eliminate metastatic tumor cells in the abdominal cavity with minimal toxic oradverse effects. When combined, tumor cell-derived vesicles can sensitize tumor cells, which facilitates the entry ofchemotherapeutics into tumor cells, thereby enhancing killing of tumor cells and limiting the risk of drug resistance. In this study, we designed a clinical trial to evaluate the safety and efficacy of intraperitoneal perfusion with tumorvesicle-encapsulated methotrexate for the treatment of cancerous ascites. Methods: Sixty patients with cancerousascites were enrolled in this open, randomized and controlled clinical trial. Participants were randomly assigned avisit number and, according to their visiting order for which a random numerical table was used, were assigned tothe trial group or the control group in a 1:1 ratio. The change in ascetic volume was used as the study outcome andadverse events were monitored during the entire length of the study. Conclusion: In this clinical trial, randomization and electronic case report forms were implemented. The trial indicated that tumorvesicle-encapsulated methotrexate was proposed to be a safe and effective method for treating malignant ascites. Our study may provide at the first time evidence for the clinical application of tumor vesicles in tumor therapy.